Sildenafil for Treatment of Microvascular Compromise in Alzheimer's Disease

Summary

This protocol plans to include a total of 25 participants. Participants will have an MRi scan with conventional sequences as well as diffusion tensor imaging (DTi), arterial-Spin-Labeling (aSL), a metabolic MRi sequence and Blood-oxygen-Level Dependent (BoLD) MRi. aSL and BoLD will be acquired at baseline and again following a single oral dose of sildenafil. BoLD MRi will be acquired under normal and hyper-capnic conditions induced by breathing room air alternating with 5% Co2 in 1 minute intervals similar to a block design functional MRi experiment. We will also collect BoLD data at rest for a functional connectivity analysis. This first part of the visit will take approximately 1 hour 30 minutes.

aSL and BoLD and metabolic MRi measures will be repeated 1 hour after the oral administration of sildenafil 50 mg. This second part of the study will take approximately 30 minutes. Sildenafil has potent effects on vascular dynamics, which are the basis of its effectiveness in treating erectile dysfunction and pulmonary hypertension.

Participant Eligibility

Cognitively impaired subjects will be included as this is inherent to the study population suffering from AD. To be included in the study, subjects will have a Clinical Dementia Rating (CDR) of either 0.5 or 1 and must have a Mini Mental Status Exam (MMSE) score of >=15 at their most recent core ADC visit, within the past year. The research staff will carefully evaluate patient and LAR understanding. The researchers will spend additional time explaining the consent form to this group of potential subjects.

Inclusion
- Primary diagnosis of AD (from the early AD cohort of the UT Southwestern ADC)
- MMSE score of >=15 (at their most recent core ADC visit, within the past year)
- CDR of either 0.5 or 1
- Must be capable and willing to undergo MRI scanning
- BP < 160/90